Project Summary Creutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative disorder caused by abnormal prion agents. Transmissibility of the non-variant (sporadic, familial, iatrogenic) forms of CJD by blood transfusion is currently unknown, while variant CJD (vCJD) has been transmitted by blood transfusion. The proposed project will continue the only active nationwide look-back study on recipients of blood products from donors subsequently diagnosed with CJD. This study began in 1995 and has been working for the past 24 years on the key objective of carefully and systematically assessing the risk of blood borne transmission of this disease in the United States. The major components of the study include collaboration with multiple sources to identify blood donors diagnosed with CJD in the United States; working with blood centers to trace the blood components from these donors to final disposition; collecting vital status and cause of death information (if applicable) on the recipients of these blood components; utilizing the data from the study to continually monitor and assess the risk of blood-borne transmission of CJD; and disseminating results of the study to relevant stakeholders. To date, the study has enrolled 76 blood donors who died of CJD and 1,000 recipients of their blood. Through 2016, 211 of these recipients were presumed to be still alive and 789 were deceased. Following transfusion, these two groups have survived a total of 4898 person-years. A total of 337 recipients survived five years or longer post transfusion and 125 of them had received blood donated 60 or fewer months before the onset of CJD in the donor. No recipients with CJD have been identified. The current results of this large, ongoing lookback study show no evidence of transfusion transmission of CJD. They reinforce the conclusion that the risk, if any, of transfusion transmission of prion disease by CJD donors is significantly lower than the comparable risk of such transmission by vCJD donors.